The temperature controlled sample carrier apparatus of the present invention was developed in connection with the automatic sampler of an automated high performance liquid chromatography apparatus and for purposes of convenience will be disclosed in this environment. It will be understood that the present invention, at least in its broader aspects, may be applied to other types of apparatus in which successive samples are to be moved relative to a work station while maintaining control of the temperature of the samples.
High performance liquid chromatography (HPLC) has gained widespread use in the past decade as a highly specific and sensitive analytic method. The use of HPLC in situations where large numbers of samples must be analyzed (e.g. quality control, pharmacokinetic and clinical laboratories) is also desirable because of the relative ease of sample preparation and the rapidity of sample analysis.
U.S. Pat. No. 3,960,003 (Beyer et al) discloses such a liquid chromatography apparatus.
To permit rapid processing of large numbers of samples in sequence automatically, an automatic sampler has been used in such liquid chromatography apparatus. Typically, the automatic sampler includes a rack carrying a circumferential array of samples and is rotatably stepped to successively present samples to a probe at a sampling station, the probe being connected to the chromatography apparatus for injection of successive samples thereinto. As set forth in the aforementioned Beyer patent, a suitable automatic sampler is that disclosed in U.S. Pat. No. 3,546,946 (Smith).
While liquid chromatographs incorporating automatic samplers for unattended injection of samples are commercially available, none is known which permits close temperature control of the samples.
Previous automatic samplers could not be used with thermally labile samples, i.e. samples which break down or undergo change upon deviation from certain temperature conditions. Accordingly, such thermally labile liquid samples were tested by hand on a one-at-a-time basis. Also, for certain solids of a type tending to degrade after a period of time in solution and wherein instability of the sample may be affected by temperature, it has been common to dissolve one sample at a time in a solvent and immediately carry out chromatographic testing of the dissolved sample before degradation could occur or be accelerated by temperature changes.
Prior automatic samplers also were not previously used in kinetic (rate of reaction) studies where temperature control is necessary during the reaction.
Prior rotating sample transports, not of the aforementioned Smith type and not necessarily suitable for chromatographic samples, have proposed generally temperature related features.
For example, U.S. Pat. No. 3,790,346 (Ritchie) discloses a testing apparatus for automatically determining prothromben times. Here, however, a single, fixed heating station is provided past which successive blood plasma samples are rotated, the heating station being flanked by first and second reagent adding stations. Thus, the purpose is to elevate the temperature of the samples sequentially, rather than to maintain temperature control of all samples simultaneously.
U.S. Pat. No. 2,418,254 (Fleharty) and U.S. Pat. No. 4,113,437 (Duff) rely on direct contact between plural sample vials and a circulating fluid, the temperature of which is intended to be controlled. However, neither of these patents is directed to chromatographic sample handling devices and both are complicated by need for a common fluid contact space for the vials, means for sealing against leakage of fluid therefrom, and vials suitable for contacting such fluid, as well as the need both for bringing of temperature controlling fluid into the container from an outside source and arrangements for circulating of the same or a different temperature controlling fluid among the vials. Moreover, problems of temperature stratification and/or uneven circulation of temperature control fluid among the vials may arise. Also, the vials are either not readily replaceable in the apparatus or have parts continuously exposed in heat exchange relation with the atmosphere.
Thus, the objects of this invention include provision of:
1. An apparatus for maintaining temperature control in a sample carrier apparatus, particularly of a type usable in the automatic sampler of an automatic high performance liquid chromatography system.
2. An apparatus, as aforesaid, capable of simultaneously maintaining a plurality of samples at a preselected temperature within close tolerances, and wherein the temperature is preselectable from a wide temperature range extending both above and below normal room temperature.
3. An apparatus, as aforesaid, capable of maintaining plural samples at a preselected constant temperature during storage remote from an automatic sampler, during installation of the sample carrier on and removal of the sample carrier from an automatic sampler, as well as during sampling in an automatic sampler.
4. An apparatus, as aforesaid, which permits rapid heat exchange between samples on the sample carrier but blocks rapid heat exchange of such samples with the surrounding atmosphere, and which substantially insulatively encloses the particular sample vial then being sampled and fully insulatively encloses the remaining sample vials on the carrier.
Other objects and purposes of this invention will be apparent to persons acquainted with apparatus of this general type upon reading the following specification and inspecting the accompanying drawings.
The objects and purposes of this invention are met by providing a temperature controlled sample carrier usable in liquid chromatography apparatus, and including a rotating sample rack having a circumferential array of upward facing sample holes adjacent the periphery for receiving sample vials and orbiting same sequentially past a sampling station. The rack is a solid cylindrical block of heat conducting material which forms a massive heat sink. An insulative cup receives the sample block and rotates therewith. A temperature control device carries a controlled temperature fluid in heat conductive contact with the central portion of the sample block and is overlaid by an insulative cover device which rotates with the block. An insulative cover ring is fixed with respect to the sampling station, overlies the array of sample holes in the block, and extends between a peripheral wall of the cup and cover device. A circumferentially narrow opening in the cover ring permits a sampling device at the sampling station access to the upper ends of sequentially presented sample vials rotating therepast with the sample block.